To identify and isolate developmental genes, we are carrying out insertional mutagenesis studies in transgenic mice derived from retrovirally infected embryonic stem (ES) cells. We have analyzed a strain segregating 23 proviruses (412 strain) to determine if any are associated with insertional mutations. We have genetic and molecular evidence that 3 of the proviruses cause recessive prenatal lethality. We have circumstantial evidence that at least one additional provirus is associated with an abnormal visible phenotype that is reminiscent of a previously defined mutation, disorganization (Ds). The molecular and phenotypic analysis of these potential insertional mutations is underway.